Local delivery of drugs can provide high local drug concentration while minimizing systemic toxicity, which can often be observed with oral dosing. However, as local depots are generally administered less frequently and include an initial burst followed by a continuous release, to maximize efficiency of therapy, it is desirable that a drug is only released when needed.
Delivering drugs to patients in a safe, effective, and compliant manner is a major challenge for the treatment of many types of disease. The ability of drugs to reach target tissues from the point of oral administration can be limited by multiple barriers including enzymatic and acidic degradation in the stomach, absorption across the intestinal epithelium, hepatic clearance, and nonspecific uptake. Effective oral dosing to achieve high concentrations of drugs within specific tissues while minimizing systemic toxicity can present a significant challenge. Conventional polymeric drug delivery systems such as implants, injectable microspheres, and patches are used by tens of millions of people annually, yet often produce a sharp initial increase in concentration to a peak above the therapeutic range, followed by a fast decrease in concentration to a level below the therapeutic range. Additionally, noncompliance with oral medication is a leading cause of hospitalizations.
The holy grail of drug delivery is an autonomous system that can titrate the amount of drug released in response to a biological stimulus, thereby ensuring that the drug is released when needed at a therapeutically relevant concentration. Such a system can rapidly release drug in response to fluctuations due to the severity of disease (this is often reflected by the local inflammatory state), patient-to-patient variability, and environmental factors.